Aims Compulsive ethanol intake, characterized by persistent consumption despite negative consequences, is an addictive behavior identified by the DSM-5 as a central criterion in diagnosing alcohol use disorders (AUD). Epidemiological data suggest that females transition from recreational alcohol use to AUD more rapidly than males. Because of this potential sex difference in the etiology of AUD, it is critical to assess addictive behaviors such as compulsive intake in both males and females in preclinical studies. Methods We used the model of aversion-resistant ethanol consumption to assess compulsive-like ethanol intake. In these experiments, C57BL6/J mice were first provided with continuous access two-bottle choice between water and ethanol to establish baseline intake. Ethanol solution was then adulterated with increasing concentrations of the bitter tastant quinine hydrochloride. Animals that consume ethanol solution despite its pairing with this negative stimulus are thought to be exhibiting compulsive-like behavior. Results We found that higher concentrations of quinine were required to suppress ethanol consumption in female mice relative to males. We found no effect of estrous cycle phase on baseline ethanol intake or on quinine-adulterated ethanol intake in females. Conclusions Collectively, these data suggest that females exhibit a higher degree of aversion-resistance than male mice. Because we observed no effect of estrous cycle phase, it is likely that the presence of threshold levels of estradiol or progesterone, as opposed to their natural fluctuation across the estrous cycle, mediates increased aversion-resistance in females. Alternatively, or in combination, developmental effects of sex hormones could contribute to aversion-resistant ethanol intake.

The opioid epidemic has become a severe public health problem, with approximately 130 opioid-induced deaths occurring each day in the United States. Prescription opioids are responsible for approximately 40% of these deaths. Oxycodone is one of the most commonly abused prescription opioids, but despite its prevalent misuse, the

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Social hierarchies are ubiquitous features of virtually all animal groups. The varying social ranks of members within these groups have profound effects on both physical and emotional health, with lower-ranked individuals typically being the most adversely affected by their respective ranks. Thus, reliable measures of social dominance in preclinical rodent models are necessary to better understand the effects of an individual's social rank on other behaviors and physiological processes. In this review, we outline the primary methodologies used to assess social dominance in various rodent species: those that are based on analyses of agonistic behaviors, and those that are based on resource competition. In synthesizing this review, we conclude that assays based on resource competition may be better suited to characterize social dominance in a wider variety of rodent species and strains, and in both males and females. Lastly, albeit expectedly, we demonstrate that similarly to many other areas of preclinical research, studies incorporating female subjects are lacking in comparison to those using males. These findings emphasize the need for an increased number of studies assessing social dominance in females to form a more comprehensive understanding of this behavioral phenomenon.

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